Inhibitory modulation is an important aspect of taste processing in the nucleus of the solitary tract (NST). Numerous in vivo and in vitro studies have demonstrated gamma-aminobutyric acid (GABA) to be an inhibitory neurotransmitter in taste processing in the NST. Recently, the influence of met-enkaphalin on taste responsive neurons in the rostral NST has been demonstrated in an in vivo model. In the present application the mechanisms through which opioids act as inhibitory neuropeptides in taste information processing in the gustatory NST are investigated. These experiments involve an in vitro brainstem slice preparation in which the activity of NST neurons that have been retrogradely labeled from the taste responsive region of the parabrachial nuclei (PbN) is recorded. These experiments test the hypothesis that both presynaptic and postsynaptic mechanisms are involved in opioid-mediated inhibition of taste activity. Clinical studies show that patients with unilateral gustatory nerve damage often report no subjective change in taste experience. The mechanisms underlying this 'taste constancy' are thought to occur centrally, most likely in the NST. Several investigators have suggested that the loss of taste information from the chorda tympani (CT) nerve is compensated by a release of inhibition on IXth nerve input. However, the possibility of compensation by taste input from the other side of the tongue has never been investigated. The hypotheses in the present application are that NST neurons receive taste information from both the ipsilateral and contralateral sides of the tongue and that the ascending pathway from the contralateral side of the tongue involves glutamatergic projections from the contralateral NST. To address these hypotheses, the PI proposes to use both a whole-animal electrophysiological preparation, within which it is possible to investigate functionally how peripheral gustatory information is carried to the contralateral NST, and an in vitro slice preparation, in which the synaptic mechanisms involved in this bilateral communication can be studied in greater detail. These studies will provide new insights into the mechanisms by which neurons in the first central taste relay are involved in modulating and processing gustatory information.